For all the successes that the checkpoint inhibitors (CPIs) have had over the past 8 years since their first approvals, and all the industry noise around partnerships and newcos in Immuno-Oncology (IO), it can seem at times that more of the talk is around what is not working in IO. The high profile failure of the IDO inhibitors, along with under-performance or safety issues with other novel MOAs being combined with CPIs, has added a strain of skepticism to what some had long felt to be an over-hyped space. Thinking of this rather as the maturing of the field, the issue still remains as to how best to move novel IO programs forward. Certainty a re-emphasis on reasonable single agent activity is a the top of correctives, but there is still more to be done in more fully interrogating the biology and doing the translational work around these novel targets and pathways, their role in combination with CPIs, and how best to position them for clinical development and for optimal patient benefit. Stay tuned for a follow-up post on my upcoming Cancer Progress session where will explore these and other aspects of moving the field forward, including biomarkers and animal models, along with interesting new MOAs and therapeutic modalities.